Chemical characterization of the inorganic fraction of aerosols and mechanisms of the neutralization of atmospheric acidity in Athens, Greece

The PM<sub>10</sub> mass concentration levels and inorganic chemical composition were determined on 12-h resolution sampling during August 2003 and March 2004, in the centre of Athens, Greece. The August 2003 campaign mean PM<sub>10</sub> mass concentration, obtained by Beta Attenuation at 5 m above ground in Athinas Street, was 56 μg m<sup>−3</sup> while the corresponding value for March 2004 was 92 μg m<sup>−3</sup>. In both campaigns the E.U. imposed daily limit of 50 μg m<sup>−3</sup> was exceeded on several days. During the March campaign, in Athinas Street, additionally obtained DSFU-PM<sub>10</sub> (PM<sub>10-2.5</sub>+PM<sub>2.5</sub>) gravimetric mass concentrations (mean: 121 μg m<sup>−3</sup>) in the "breathing zone", at 1.5 m above ground were significantly higher compared to the respective mean PM<sub>10</sub> mass concentrations obtained by the same method at 25 m above ground, in a second site (AEDA; mean: 86 μg m<sup>−3</sup>) also in the centre of the city. The above findings suggest that, for a realistic estimation of the exposure of citizens to particulate matter, PM<sub>10</sub> sampling in the "breathing zone" (1.5–3 m above ground) is necessary. Such data are presented for the first time for the centre of Athens. In both campaigns, calcium was found to be the predominant component of the coarse fraction while crust-related aluminosilicates and iron were the other major components. The above elements constitute the most important components of the fine fraction, together with the predominant sulphur. All toxic metals were found in concentrations below the established air quality limits, and most of them in lower concentrations compared to older studies. Lead in particular, appeared mostly in the fine fraction and in very low concentrations compared to studies dating more than a decade back. The predominant ions of the coarse fraction have been found to be Ca<sup>2+</sup>, NO<sub>3</sub><sup>−</sup>, Na<sup>+</sup> and Cl<sup>−</sup>, while SO<sub>4</sub><sup>2−</sup>, Ca<sup>2+</sup> and NH<sub>4</sub><sup>+</sup> were the major ionic components of the fine fraction. In the fine particles, a low molar ratio of NH<sub>4</sub><sup>+</sup>/SO<sub>4</sub><sup>2−</sup> indicated an ammonium-poor ambient air, and together with inter-ionic correlations suggested that atmospheric ammonia is the major neutralizing agent of sulfate, while being insufficient to neutralize it to full extend. The formation of NH<sub>4</sub>NO<sub>3</sub> is therefore not favored and additional contribution to the neutralization of acidity has been shown to be provided by Ca<sup>2+</sup> and Mg<sup>2+</sup>. In the coarse particle fraction, the predominantly abundant Ca<sup>2+</sup> has been found to correlate well with NO<sub>3</sub><sup>−</sup> and SO<sub>4</sub><sup>2−</sup>, indicating its role as important neutralizing agent in this particle size range. The proximity of the location under study to the sea explains the important concentrations of salts with marine origin like NaCl and MgCl<sub>2</sub> that were found in the coarse fraction, while chloride depletion in the gaseous phase was found to be limited to the fine particulate fraction. Total analyzed inorganic mass (elemental+ionic) was found to be ranging between approximately 25–33% of the total coarse particle mass and 35–42% of the total fine particle mass

Chemical characterization of the inorganic fraction of aerosols and mechanisms of the neutralization of atmospheric acidity in Athens, Greece

International audienceMass concentration levels and the inorganic chemical composition of PM10 (two fractions; PM10?2.5 and PM2.5) were determined during August 2003 and March 2004, in the centre of Athens, Greece. August 2003 monthly mean PM10 mass concentration, at 5 m above ground, was 56 ?g/m3 and the EU imposed daily limit of 50 ?g/m3 was exceeded on 16 occasions. The corresponding monthly mean for March 2004 was 92 ?g/m3 and the aforementioned daily limit was exceeded on 23 occasions. The PM10 (PM10?2.5+PM2.5) mass concentrations at 1.5 m above ground were found to be approximately 20% higher compared to the respective PM10 measured at 5 m. Consequently, for a realistic estimation of the exposure of citizens to particulate matter, PM10 sampling at a height of 1.5?3 m above ground, in the "breathing zone" is necessary. Such data are presented for the first time for the centre of Athens. In both campaigns, calcium was found to be the predominant component of the coarse fraction while crust-related aluminosilicates and iron were found to be the other major components of the same fraction. The above elements constitute the most important components of the fine fraction, together with the predominant sulphur. Toxic metals were found to be below the air quality limits and in lower concentrations compared to older studies, with the exception of Cu and V for which some increase was observed. Pb, in particular, appeared mostly in the fine fraction and in very low concentrations compared to studies dating more than a decade back. The major ions of the coarse fraction have been found to be Ca2+, NO3? and Cl?, while SO4?2, Ca2+ and NH4+ were the major ionic components of the fine fraction. The low molar ratio of NH4+/SO4?2 indicated an ammonium-poor ambient air, where atmospheric ammonia is not sufficient to neutralize all acidity and the formation of NH4NO3 does not occur to a significant extend. Calcium predominated the coarse fraction and its good correlations with NO3? and SO4?2 indicated its role as an important neutralizing agent of atmospheric acidity in this particle size range. In the fine fraction, both Ca2+ and NH4+ participate in the neutralizing processes with NH4+ being the major neutralizing agent of SO4?2. Chloride depletion from NaCl or MgCl2 was not found to occur to a significant extend. Total analyzed inorganic mass (elemental+ionic) was found to be ranging between approximately 25?33% of the total coarse particle mass and 35?42% of the total fine particle mass

Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach

Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47 % were disease-associated polymorphisms, 26 % disease-associated polymorphisms with additional supporting functional evidence, 19 % functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4 % putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3 % disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55

Mucopolysaccharidosis VI

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B leading to the accumulation of dermatan sulfate. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (generally >100 μg/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 μg/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS VI, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. Diagnosis generally requires evidence of clinical phenotype, arylsulfatase B enzyme activity <10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS I, II IVA, VII), sialidosis and mucolipidosis. Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme®), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided

The Gag Cleavage Product, p12, is a Functional Constituent of the Murine Leukemia Virus Pre-Integration Complex

The p12 protein is a cleavage product of the Gag precursor of the murine leukemia virus (MLV). Specific mutations in p12 have been described that affect early stages of infection, rendering the virus replication-defective. Such mutants showed normal generation of genomic DNA but no formation of circular forms, which are markers of nuclear entry by the viral DNA. This suggested that p12 may function in early stages of infection but the precise mechanism of p12 action is not known. To address the function and follow the intracellular localization of the wt p12 protein, we generated tagged p12 proteins in the context of a replication-competent virus, which allowed for the detection of p12 at early stages of infection by immunofluorescence. p12 was found to be distributed to discrete puncta, indicative of macromolecular complexes. These complexes were localized to the cytoplasm early after infection, and thereafter accumulated adjacent to mitotic chromosomes. This chromosomal accumulation was impaired for p12 proteins with a mutation that rendered the virus integration-defective. Immunofluorescence demonstrated that intracellular p12 complexes co-localized with capsid, a known constituent of the MLV pre-integration complex (PIC), and immunofluorescence combined with fluorescent in situ hybridization (FISH) revealed co-localization of the p12 proteins with the incoming reverse transcribed viral DNA. Interactions of p12 with the capsid and with the viral DNA were also demonstrated by co-immunoprecipitation. These results imply that p12 proteins are components of the MLV PIC. Furthermore, a large excess of wt PICs did not rescue the defect in integration of PICs derived from mutant p12 particles, demonstrating that p12 exerts its function as part of this complex. Altogether, these results imply that p12 proteins are constituent of the MLV PIC and function in directing the PIC from the cytoplasm towards integration

Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality

HIV infection of non-dividing cells: a divisive problem

Understanding how lentiviruses can infect terminally differentiated, non-dividing cells has proven a very complex and controversial problem. It is, however, a problem worth investigating, for it is central to HIV-1 transmission and AIDS pathogenesis. Here I shall attempt to summarise what is our current understanding for HIV-1 infection of non-dividing cells. In some cases I shall also attempt to make sense of controversies in the field and advance one or two modest proposals

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Factors associated with HIV testing and HIV treatment adherence: A systematic review

Background: The impact of the global economic crisis on HIV-related access and care remains unclear. The objective of this systematic review of the literature was to evaluate the association between socioeconomic factors and HIV diagnosis, and adherence to treatment, following the 2008 global economic crisis. Method: A systematic search of PubMed and Scopus for studies published between January 2008 and October 2016 was conducted. Studies providing data on social, demographic, economic and cultural barriers associated with HIV diagnosis and treatment were included. Results: Of 33 studies included, 22 evaluated HIV testing and 11 evaluated treatment adherence. Medical history of a sexually transmitted disease, knowledge of HIV-related risks, and age, were significantly associated with HIV testing in most of the included studies. Absence of social support, and alcohol or substance use, were the most common factors associated with adherence. Financial factors were not as commonly found to be related to access to HIV diagnosis and HIV treatment adherence, compared to knowledge of HIV-related risks and social support. Conclusion: The identification of persons who are less likely to test for HIV, and to adhere to HIV treatment, may serve as a guide for public health interventions, especially in resource-limited areas. © 2017 Bentham Science Publishers